The group A streptococcal M protein is a surface molecule that allows the organism to resist attack by human phagocytic cells and thus is a major virulence factor for the streptococcus. Type specific antibodies to the M molecules coating the cell surface are able to protect against streptococcal infection. To date there are over 70 immunologically different M proteins found in nature. Our studies have established that the M molecule is composed of two alpha-helical protein chains wound together to form a coiled- coil fibril extending about 600 A from the cell surface. DNA sequence analysis has established the complete sequence of the M protein from M6 streptococci. We have also found, for the first time, that epitopes in the C-terminal half of the protein (proximal to the cell wall) are conserved. With this information, we wish to synthesize peptides representing the majority of the M molecule to determine if antibodies to more conserved regions allow for phagocytosis of several serotypes. The human immune response to the complete M protein will be examined to determine if certain regions are more immunodominant than others and how this relates to functional (antiphagocytic) regions of the protein. A high proline and glycine containing protein, present on a streptococcal pyoderma strain, will be isolated and examined for its presence on other pyoderma strains and ability to promote adherence in the skin. These studies may answer questions regarding the difference between pyoderma and pharyngitis strains. Little is known concerning the secretory immune response to the M protein and its ability to influence colonization and infection. A mouse model of upper respiratory infection and carrier state, using a naturally infecting group A streptococcal strain for mice, will be used to examine the protective effects of SIgA in the upper respiratory tract. Antigenic drift may be the way in which streptococci are able to change their M types. We will examine this question in the mouse by using antibodies to specific opsonic determinants. We will attempt to select for streptococcal mutants having changes in opsonic determinants induced by immunological pressure. The studies outlined will allow us to better understand the M protein immunochemically, which may enable us to design strategies to protect against infection by multiple streptococcal serotypes.